A rare missense variant in the milk fat globule-EGF factor 8 (MFGE8) increases T2DM susceptibility and cardiovascular disease risk with population-specific effects

2020 ◽  
Vol 57 (6) ◽  
pp. 733-741
Author(s):  
Bishwa R. Sapkota ◽  
Dharambir K. Sanghera
Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Ahlia Sekkarie ◽  
Janet Figueroa ◽  
Caroline Um ◽  
Jean Welsh

Background: Dietary guidelines recommend consumption of 1% or skim (i.e. non-fat) milk for children >2 years due to concerns about the role of saturated fat in raising low-density lipoprotein cholesterol (LDL) levels and cardiovascular disease risk. Low- or non-fat milk is also recommended to promote energy balance and reduce obesity risk. While more recent evidence in adults suggests no association between milkfat and cardiovascular disease risk, this association has not been well studied among children who tend to be the highest consumers of milk. No known studies have demonstrated an association between milkfat consumption and lipid levels in children. Our objective was to determine if there is an association between milk fat consumption and risk of dyslipidemia and obesity among U.S. children. Methods: We used cross-sectional data from children 2-19 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 (n=7261). Usual milkfat intake (i.e. never/rare milk consumption, non-fat, 1%, 2%, or whole) was self-reported by parent or child. Lipid levels (12-19 years only) and adiposity (BMI z-score and weight category [underweight, normal, overweight, or obese] in all ages) were assessed by trained staff using standardized methods. Covariates included child age, sex, household income, race/ethnicity, physical activity, dieting, and total energy intake. We used multivariate linear and logistic regression models to examine the association between milkfat consumption and our outcomes and conducted pairwise comparisons to assess differences between different milkfat consumers. Results: Most children consumed 2% milk (42.3%), followed by whole (26.1%), 1% milk (11.7%), never/rare consumption (10.2%), and nonfat (9.7%). We found no significant trends in mean cholesterol (total, HDL, LDL) with consumption of milk with greater fat content. There was a significant trend towards higher triglycerides as milkfat intake increased (p=0.01) though this association was stronger among 2% milk compared to whole fat consumers. We found no significant trend in prevalence of each BMI category across milk fat intake. Pairwise comparisons demonstrated that usual consumption of 1% and 2% milkfat was associated with both higher BMI Z-score and odds of obesity compared to whole milk. Conclusion: We found no significant linear trend between usual %milk fat consumed and indicators of cardiovascular disease (BMI-Z and lipid levels) in children, except for triglycerides which rose as milkfat intake increased. However, triglycerides were higher among the 2% compared to whole milkfat consumers. Overall, whole milk was not associated with increased indicators of cardiovascular disease risk in children.


2009 ◽  
Vol 48 (4) ◽  
pp. 191-203 ◽  
Author(s):  
J. Bruce German ◽  
Robert A. Gibson ◽  
Ronald M. Krauss ◽  
Paul Nestel ◽  
Benoît Lamarche ◽  
...  

2022 ◽  
Author(s):  
Emil Jørsboe ◽  
Mette Korre Andersen ◽  
Line Skotte ◽  
Frederik Filip Stæger ◽  
Nils Joakim Kaas Færgeman ◽  
...  

Background: The common Arctic specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this we aimed to investigate the effect of p.G137S on metabolic health, and cardiovascular disease risk among Greenlanders to quantify its impact on the population. Methods: In a population based Greenlandic cohort (n=5063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. Additionally, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n=1629). Results: 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischaemic heart disease (HR (95% CI), 1.51 (1.18-1.92), P=0.00096), peripheral artery disease (1.69 (1.01-2.82), P=0.046), and coronary operations (1.78 (1.21-2.62), P=0.0035). Conclusions: Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.


2001 ◽  
Vol 01 (4) ◽  
pp. 175-183
Author(s):  
Kate Wheeler ◽  
Cora E. Lewis ◽  
Dale Williams ◽  
Stephen Sidney ◽  
Catarina I. Kiefe ◽  
...  

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